Aminoalkyl-ethano-anthracenes



United States Patent 3,399,201 AMINOALKYL-ETHANO-ANTHRACENES PaulSchmidt, Therwil, Max Wilhelm, Allschwil, and Kurt Eichenberger,Therwil, Switzerland, assignors to Ciba Corporation, New York, N.Y., acorporation of Delaware No Drawing. Continuation-impart of applicationSer. No. 404,904, Oct. 19, 1964, and is a continuation-in-part ofapplication Ser. No. 512,201, Dec. 7, 1965. This application Apr. 12,1966, Ser. No. 541,979

Claims priority, application Switzerland, Nov. 29, 1960, 13,359/60; Oct.10, 1961, 11,710/61; Nov. 1, 1963, 13,434/63; Dec. 23, 1964, 16,637/64;Nov. 24, 1965, 16,177/65; Dec. 10, 1965, 17,086/65 25 Claims. (Cl.260268) The present application is a Continuation-impart of ourapplication Ser. No. 404,904, filed Oct. 19, 1964, which is acontinuation-in-part of our application Ser. No. 151,198 filed Nov. 9,1961, and of our application Ser. No. 512,201 filed Dec. 7, 1965, allnow abandoned.

The present invention concerns9-aminoalkyl-9:l0-dihydro-9:10-ethano-(l:2)-anthracenes containing thenucleus of the formula as well as of their quaternary ammoniumderivatives and salts.

In the new compounds the amino group of the aminoalkyl residue may beunsubstituted, but it is preferably monosubstituted or disubstituted.Particularly suitable substituents are lower hydrocarbon residues whichmay be interrupted by hetero atoms such as oxygen, sulphur or nitrogen,and/or may be substituted by free hydroxyl, amino or mercapto groups orby halogen atoms such as fluorine, chlorine, bromine or iodine. As lowerhydrocarbon residues there may be mentioned above all: lower alkyl oralkenyl groups such as methyl, ethyl, propyl, or isopropyl; straight orbranched butyl, pentyl, hexyl, or heptyl radicals bound in any desiredposition; allyl or methallyl radicals unsubstituted or alkyl-substitutedcycycloalkyl or cyclo-alkenyl groups such as cyclopentyl, cyclohexyl,cycloheptyl, cyclopentenyl, cyclohexenyl groups; unsubstituted orakyl-substituted cycloalkyl-alkyl or cycloalkenyl-alkyl groups such ascyclopentylor cyclohexenyl-methyl, -ethyl or -propyl groups; aralkyl oraralkenyl such as phenyl-methyl, -ethyl, vinyl or propyl groups; oraryl, more especially phenyl radicals; or alkylene or alkenylene groupssuch, for example as butylene- (1:4) pentylene-(l :5),1:5-dimethylpentylene-( 1 :5), hexylene-(lz6) and hexylene-(lzS).Residues of this kind interrupted by hetero atoms are, for example,alkoxyalkyl or oxa-cycloalkyl-alkyl groups such as methoxyethyl,ethoxyethyl propoxyethyl, butoxyethyl, methoxypropyl,methoxyethoxyethyl, tetrahydrofurylmethyl, methylmercaptoethyl, oxa-,azaor thia-alkylene or -alkenylene residues such :as 3-aza-, oxaorthia-pentylene-(lz 5), 3-azahexylene (1:6), 1:5dimethyl-3aza-pentylene-(l:5 3- methyl 3 aza-pentylene-( l :5), or3-hydroxyethyl-3-azapentylene-(lcS). The amino group is above all amonoor di-lower alkyl-amino group such as the methylamino, ethylamino,n-butylamino, dimethylamino, diethylamino, dipropylamino,N-methyl-N-ethylamino group, or an N- lower .alkyl-N-cycloalkylaminogroup such as the N-methyl-N-cyclopentyl or cyclohexyl group; or apyrrolidino, piperidino, morpholino or thia-morpholino groups such asthe pyrrolidino, piperidino, morpholino, piperazino, N-

methyl-, N-ethylor N-,8-hydroxy-ethyl-piperazino group.

The fourth substituent on a quaternary ammonium group is above all alower alkyl or alkenyl group such as a methyl, ethyl, allyl, propyl orbenzyl group or a phenoxy-lower alkyl such as the phenoxyethyl group.

The alkylene residue which connects the aforementioned amino group withthe anthracene nucleus is above all a lower unbranched or branchedalkylene group which preferably contains 1 to 4 carbon atoms such, forexample :as a methylene, ethylene-(1:2), propylene-(1 :2),propylene-(1:3), butylene-(lzZ), butylene-(1:3), butylene-(2z3) orbutylene-(1z4) residue.

The new compounds can be further substituted, for example, in positions1 to 8 of the anthracene ring or on other aromatic rings by lower alkyl,alkoxy, alkenyloxy or alkylrnercapto groups, by halogen atoms such asfluorine, chlorine, bromine or iodine or by the pseudohalogentrifluoromethyl, by alkylsulphonyl, alkanoyl, nitro or amino groups, andin this connection there may be mentioned as alkyl groups, for example,methyl, ethyl, propyl, isopropyl, butyl, isobutyl, or tertiary butyl; asalkoxy or alkenyloxy groups the methoxy, ethoxy, allyloxy ormethylenedioxy group; as alkylmercapto the methylmercapto orethylmercapto group; and as alkanoyl groups above all the acetyl,propionyl or butyryl residue. In position 10 the new compounds maycontain above all an aliphatic hydrocarbon residue such as one of theabovementioned lower alkyl or alkenyl groups, or a halogen atom.

The new compounds have valuable pharmacological properties; inter aliathey display an inhibitory action on the central nervous systemcharacterized by an antagonism towards psychomotoric substances such,for example, as mescalin, and inhibit the transmission of spinalreflexes; and they can therefore be used as tranquilizers in humanmedicine. They are also suitable as additives to animal fodder, sincethey bring about a better intake.

In addition, the new compounds may be used as starting material orintermediates for the preparation of other Valuable compounds.

Of special value are the 9-aminomethyland 9-aminopropyl 9: 10-dihydro-9:lO-ethano-(l:2)-anthracenes and their salts and amongst them especiallythose in which the amino group is secondary or tertiary, preferablybeing a monoor di-lower alk-yl amino or cycloalkylamino, pyrrolidino,piperidino, morpholino, piperazino, N-methylpiperazino, Nethylpiperazino or N ,8 hydroxy-ethylpiperazino group.

Special mention deserve the compounds of the formula and and theirsalts, in which A represents a secondary or tertiary amino group, moreespecially one of the last-mentioned amino groups, especially adimethylaminoor methylamino group. Of primary importance are 9-methylamino-methyl-, 9-n-butylamino-methyl-, 9-dimethylaminomethylor 9diethylarnino-methyl-9:10-dihydro-9:10- ethano-( 1 :2)-anthracene, 9-'-dimethylamino-propyl-9: 10- dihydro-9: 10-ethano-( l :2) -anthracene,9-y-methylaminopropyl-9:l0-dihydro-9:10-ethano-(l:2)-anthracene and 9--(N hydroxyethyl-piperazino)-propyl]-9:IO-dihydro- 9:IO-ethano-(l:2)-anthracene and their salts.

The new compounds are prepared by such known methods.

Thus, for example, a residue convertible into an aminoalkyl orammonium-alkyl group, present in position 9 of a9:10-dihydro-9:10-alkano-( l:2)-anthracene may be so converted. Aresidue convertible into an aminoalkyl or anrmoniumalkyl group is forexample one which is convertible into an aminoalkyl group by reduction,for example carbarnyl, or carbamylalkyl groups which can be reduced inconventional manner, advantageously with lithium-aluminium hydride or asimilar reducing agent for amides, to form the corresponding aminoalkylgroups.

Similarly, nitroalkyl, nitroalkenyl, cyano or cyanoalkyl groups can bereduced to the corresponding aminoalkyl groups, the reduction of saidgroupings being carried out with the use of a conventional agent such,for example as activated hydrogen, more especially catalyticallyactivated hydrogen. Catalysts particularly suitable for this purpose areRupe or Raney nickel, or platinum or palladium catalysts.

Further groups that can be reduced to aminoalkyl groups are iminoalkylresidues or the corresponding amino-hydroxy-alkyl residues which can beconverted into the aminoalkyl residues with the use of a conventionalreducing agent, primarily a metal hydride, for example a dilight metalhydride, such as alkali metal borohydride, or catalytically activatedhydrogen, for which purpose platinurn oxide and Raney nickel areespecially suitable catalysts. As iminoalkyl residues there aresuitable, apart from the usual Schitfs bases, also hydroxyimino-alkylgroups.

According to another process the 9:10-ethano-(lz2) residue is introducedin conventional manner into a 9- a minoalkyl-anthracene, or into aquaternary ammonium derivative or a salt thereof, advantageously withthe use of ethylene, by the Diels-Alder method; depending on thereactivity of the anthracene compound this reaction may have to becarried out at an elevated temperature and/or under superatmosphericpressure and/or in the presence of a catalyst.

In a resulting primary, secondary or tertiary amino group furthernitrogen substituents may be introduced in known manner, for example bytreatment with a reactive ester, for example one of those mentionedabove, or with a corresponding alcohol, or by reductive alk-ylation withthe use of an appropriate carbonyl compound or by acylation withcarboxylic acids or their functional derivatives and reduction of theobtained N-acyl compounds.

Furthermore, Substituents may be introduced into the benzene nuclei,such as nitro groups, which may be effected by nitration. Substituentspresent in the molecule can be converted in the conventional manner, forexample nitro groups on the aromatic residues may be reduced to aminogroups.

The invention further includes any variant of the pres ent process inwhich an intermediate obtained at any stage of the process is used asstarting material and/or the remaining step or steps is/ are carriedout; or the process is discontinued at any stage thereof; or in which astarting material is formed in the course of the reaction, or used inthe form of a quaternary ammonium compound or a salt thereof. Thus, forexample, the starting material may be a 9 oxoalkyl-9: l-dihydro-9:10-ethano-( l :2)-anthracene, for example a 9 formyl or 9 formylalkylcompound, which is treated under suitable reducing conditions, forexample those mentioned above for reducing iminoalkyl groups, withammonia or with a primary or secondary amine, which procedure yields asintermediate one of the aforementioned iminohydroxy or aminohydroxycompounds.

The aforementioned reactions are carried out in the usual manner in thepresence or absence of diluents, condensing agents and/or catalysts, atroom ,temperature or a lower or higher temperature, if desired undersuperatmospheric pressure.

The starting materials are known or can be prepared by known methods.Any new starting materials used are likewise included in the invention.

Depending on the reaction conditions and starting material used the newcompounds are obtained in the free form or in the form of salts thereof.The salts of the new compounds can be converted in known manner into thefree compounds, for example acid addition salts by reaction with a basicagent. On the other hand, a resulting free base may form salts withinorganic or orgainc acids. Acid addition salts are preferablymanufactured with therapeutically useful acids, for example a hydrohalicacid such as hydrochloric or hydrobromic acid, perchloric, nitric orthiocyanic acid, a sulphuric or phosphoric acid, or an organic acid suchas formic, acetic, propionic, glycollic, lactic, pyruvic, oxalic,malonic, succinic, maleic, fumaric, malic, tartaric, citric, ascorbic,hydroxymaleic, dihydroxymaleic, benzoic, phenylacetic, 4-amino-benzoic,4-hydroxybenzoic, anthranilic, cinnamic, mandelic, salicyclic,4-aminosalicyclic, 2-phenoxybenzoic, Z-acetoxybenzoic, methanesulphonic,ethanesulphonic, hydroxyethanesulphonic, benzenesulphonic,para-toluene-sulphonic, naphthalenesulphonic or sulphanilic acid;methionine, tryptophan, lysine or arginine. The salts may be monosaltsor polysalts.

Quaternary ammonium salts may also be converted into the ammoniumhydroxides, for example by treatment of an ammonium halide with freshlyprecipitated silver oxide, or by treating an ammonium sulphate withbarium hydroxide solution, or with the use of a basic ion-exchanger, andfrom the resulting ammonium hydroxide other ammonium salts can beprepared by reaction with an acid, for example one of those mentionedabove. If desired, this exchange may also be carried out directly withthe use of a suitable ion-exchanger.

The new compounds are intended to be used as medicaments in the form ofpharmaceutical preparations containing them in conjunction with apharmaceutical or ganic or inorganic, solid or liquid excipient suitablefor enteral (for example oral) or parenteral administration. Suitableexcipients are substances that do not react with the new compounds such,for example, as water, gelatine, lactose, starch, magnesium stearate,talc, vegetable oils, benzyl alcohols, gums, polyalkylene glycols,cholesterol or other known medicinal excipients. The pharmaceuticalpreparations may be, for example, tablets, dragees 0r capsules, or inliquid form solutions, suspensions or emulsions. They may be sterilisedand/or may contain assistants such as preserving, stabilising, wettingor emulsifying agents, salts for regulating the osmotic pressure orbuffers. The dosage of the new compounds may vary according to theparticular compound and the particular needs of the patient. Usually itis the range of 25500 mg. daily, for example between and 300 mg; thedose may be divided and thus administered twice or three times a day.They may also contain other therapeutically valuable substances.

The new compounds may also be used in veterinary medicine, for examplein one of the forms mentioned above, or in the raising and feeding ofanimals in the form of fodders or as additives to animal fodder, forexample in admixture with the conventional extenders and diluents andfeeding stuffs respectively.

The following examples illustrate the invention.

Example 1 A solution of 9.0 grams of 9:10-dihydro-92l0-ethano-(1:2)-anthracene-(9)-carboxylic acid diethylamide in 50 cc. oftetrahydrofuran is stirred dropwise at room temperature into asuspension of 2.5 grams of lithium aluminium hydride in cc. oftetrahydrofuran. The mixture is heated for 3 hours at the boil and thencooled in ice. The organ0-n1etal complexes and the excess oflithium-aluminium hydride are decomposed by carefully dropping in 2.5cc. of water, 2.5 cc. of sodium hydroxide solution of 15% strength and7.5 cc. of water. The granular precipitate formed is filtered OE and thesolvent is evaporated, to yield 9-diethylamino-methyla Qz which melts at112 to 115 C. after having been recrystallised from ehtanol. Itshydrochloride melts at 243 to 245 C. Y

The 9: l dihydro-9: IO-ethano-(l:2)-anthracene (9)- car-boxylic aciddimethylamide used as starting material is prepared in the followingmanner:

A mixture of 10.0 grams of 9: 10-dihydro-9: l0-ethano-(l:2)-anthracene-(9)-carboxylic acid and 100 cc. of thionyl chloride isrefluxed for 6 hours; the thionyl chloride is then evaporated to leavean oil which crystallises when left to itself for some time.Recrystallis'ation from petroleum ether yields the 9: 10-dihydro-9:10-ethano-(l:2)- anthracene-(9)-carboxylic acid chloride of the formulain crystals melting at 72 to 75 C.

10.0 grams of diethylamine in 25 cc. of benzene are vigorously stirreddropwise at room temperature into grams of the acid chloride in 50 cc.of benzene. The mixture is stirred for 2 hours at 40 C. and thenextracted with water. On evaporation of the benzene an oil remains whichcrystallises slowly. Recrystallization from aqueous methanol yields the9:10-dihydro-9:10-ethano-(1:2)-anthracene-(9)-carboxylic aciddiethylamide of the formula in crystals melting at 108 to 109 C.

Example 2 A mixture of 10.0 grams of 9:10-dihydro-92l0-ethano-(1:2)-anthracene-(9)-aldehyde, 6.0 grams of fi-phenylethyl-amine and 150cc. of benzene is boiled for 2 hours with the use of a water separator,whereupon the benzene is evaporated in vacuo. The residue is dissolvedin 200 cc. of ethyl acetate, treated with 2 grams of Raney nickel andhydrogenated at room temperature under atmospheric pressure. Thecatalyst is then filtered off and the solvent evaporated, the residuebeing treated with 100 cc. of 2 N-hydrochloric acid, whereuponcrystallisation sets in to yield the 9-(B-phenylethylaminomethyl)-9:l0-dihydro-9:10-ethano-(1:2)-anthracene hydrochloride 0 the formula whichmelts at 253 to 255 C. after having been recrystallised fromethanol+ether.

The 9: 10-dihydro-9: 10-ethano-( 1 :2)-anthracene-(9) aldehyde used asstarting material is prepared as follows:

A solution of 50 grams of anthracene-(9)-aldehyde in 200 cc. ofdimethylformamide is heated in an autoclave with ethylene to 170 C., thewhole is cooled after 24 hours, and the solvent is evaporated in awater-jet vacuum. The residue is dissolved in a small amount ofchloroform. On addition of ethanol the 9: lO-dihydro-9z10-ethano-(1:2)-anthracene-(9)-aldehyde of the formula crystallises in the form ofprisms melting at 106 to 107 C.

Example 3 which melts at 76 to 78 C. after having been recrystallisedfrom ethanol.

Example 4 A solution of 10 grams of 9:10-dihydro-9:10-ethano-(l:2)-anthracene-(9)aldehyde and 10 grams of monomethylamine in 1 00 cc.of ethanol is heated at 80 C. for 4 hours in an autoclave. The reactionmixture is then evaporated to dryness under reduced pressure to leave acrystalline residue which is dissolved in 150 cc. of ethanol and, afterthe addition of 2 grams of Raney nickel, hydrogenated at 40 C. underatmospheric pressure. When the absorption of hydrogen has subsided, thecatalyst is filtered ofi and the filtrate evaporated under reducedpressure. An oil remains which is covered with 100 cc. of 2N-hydrochloric acid. The9-methylaminomethyl-9':l0-dihydro-9:10-ethano-(1:2)-anthracenehydrochloride of the formula Gri -M443 0 H01.

crystallises immediately; after crystallization from methanol it meltsat 32=0-322 C.

Example 5 A mixture of 10 grams of 9-methylamino-methyl-9z10- dihydro9:10 ethano (1:2) anthracene, 4 cc. of aqueous formaldehyde solution of30% strength and 50 cc. of formic acid is heated at C. for 5 hours.After cooling, the reaction mixture is rendered alkaline by the additionof 2 N-sodium hydroxide solution. The oil which has separated isextracted with methylene chloride and the extract evaporated. Thereremains 9-methylaminomethyl-9:10-dihydro-9:10-ethano-(1:2)-anthracene ofthe formula CHE-NEH;

which melts at 7880 C. after crystallization from ethanol; itshydrochloride melts at 233234 C. In an analogous manner from9-(n-butylamino-methyl)-9;10-dihydro 9z -ethano-(l:2)-anthracene thereis obtained 9-(N- methyl N n butylamino methyl) 9:10 dihydro-9:10-ethano-(1:2)-anthracene melting at 257 C. hydrochloride.

Example 6 A solution of 17.8 grams ofN-acetyl-9-methylaminomethyl-9:10-dihydro-9:IO-ethano-(l:2)-anthracenein 50 cc. of tetrahydrofuran is added dropwise, with stirring to 4 gramsof lithium-aluminium hydride in 100 cc. of tetrahydrofuran. The mixtureis then stirred for 2 hours at 50 C. 4 cc. of water, 4 cc. of sodiumhydroxide solution of strength and 12 cc. of Water are then added to thereaction mixture, the precipitate formed is filtered with suction andthe filtrate evaporated to dryness under reduced pressure to yield9-(methyl-ethylamino-methyl)- 9:1(Ldihydro-9zl0-ethano (1:2) anthraceneof the formula which melts at 77-79 C. after crystallization frommethanol; its hydrochloride melts at 235-236 C.

The N-acetyl 9 methylamino-methyl-9:10-dihydro-9:10-ethanol-(1:2)-anthracene used as starting material may be preparedin the conventional manner by acetylating 9methylamino-9:10dihydro-9:10-ethano-(1:2)-anthracene with acetylchloride in pyridine. The compound melts at 128 C. afterrecrystallization from ethanol.

Example 7 10 grams of 9-cyano-9:10-dihydro-9:10-ethano-(1:2)- anthraceneare dissolved in 200 cc. of ethanol. The solution is saturated withammonia and after the addition of 2 grams of Raney nickel hydrogenatedat 70 C. under 70 atmospheres gauge pressure. When the absorption ofhydrogen has subsided, the catalyst is filtered off and the filtrateevaporated to dryness under reduced pressure. The residue is treatedwith 2 N-hydrochloric acid, the hydrochloride of 9-aminomethyl 9: 10dihydro-9z10- ethano-(1:2)-anthracene of the formula CHE-N112 ac;

precipitating in the form of crystals melting at 313- Example 8 Ethyleneis introduced into a solution of 10 grams of9-dimethylamino-methyl-anthracene in 300 cc. of benzene in an autoclaveup to atmospheres gauge pressure, and the mixture is then heated for 12hours at 170 C.

After the reaction has ceased, the benzene solution is extracted with 2N-hydrochloric acid, the acidic extract rendered alkaline by theaddition of sodium hydroxide solution, and the precipitated baseextracted with methylene chloride. After drying and evaporation of thesolvent there remains 9 dimethylamino-methyl-9: IO-dihydro-9:10-ethano-(1:2)-anthracene of the formula which is converted into itshydrochloride of MP. 234 C. by the addition of ethanolic hydrochloricacid and diethyl-ether.

The 9-dimethylamino-methyl-anthracene used as ing material may beprepared as follows:

20 grams of 9-chloromethyl-anthracene are heated with 10 grams ofdimethylamine in 100 cc. of ethanol for 5 hours in an autoclave at 100C. The reaction mixture is then evaporated to dryness under reducedpressure, the residue dissolved in ether and the solution extracted with2 N-sodium hydroxide solution. After drying and evaporation of theethereal solution there is obtained 9-dimethylamino-methyl-anthracenewhich after crystallization from ethanol melts at -66 C.

start- Example 9 12 grams of fl-[9:10-dihydro-9:10-ethano-(1:2)-9-anthryl]-propionic acid dimethylamide in 50 cc. of tetrahydrofuran areadded dropwise with stirring at room temperature to a suspension of 3.5grams of lithiumaluminium-hydride in cc. of dry tetrahydrofuran; themixture is then boiled under reflux for 2 hours. 4 cc. of water and 10cc. of sodium hydroxide solution of 15% strength are then added dropwiseWhile cooling with ice. and the precipitate which settles out isfiltered. The filtrate is evaporated to dryness under reduced pressure,the oily residue dissolved in ether and the ether solution extractedwith 2 N-hydrochloric acid. The acidic solution is rendered alkaline bythe addition of 10 N-sodium hydroxide solution and the precipitated baseextracted with ether. After drying and evaporation of the extract thereis obtained 9-y-dimethylamino-propyl-9z l0-dihydro- 9:IO-ethano-(l:2)-anthracene of the formula which melts at 8890 C. aftersublimation; its hydrochloride melts at 205206 C.

The B [9: 10-dihydro-9: l0 ethano-(1:2)-9-anthryl]- propionic aciddimethylamide used as starting material may be prepared as follows:

A solution of 10 grams of fl-(9-anthryl)-propionic acid (prepared asdescribed by F. H. C. Stewart, Australian Journal of Chem., 13, 483(1960)) in 200 cc. of dimethylformamide is saturated with ethylene andthe mixture heated in an autoclave for 24 hours at C. After cooling, 500cc. of water are added the precipitate formed filtered off. Theprecipitate is recrystallized from ethanol to yield B-[9z 10-dihydro-9':IO-ethano-(l :2)-9-anthry1]- propionic acid of the formula CH CH COOL-1in the form of crystals melting at 218-219 C.

10 grams of the above acid are boiled with 500 cc. of thionyl chloridefor 4 hours and the mixture evaporated to dryness under reduced pressureto yield a crystalline residue which is dissolved in 50 cc. of benzene.To this solution there is added dropwise at room temperature, withstirring, a solution of grams of dimethylamine in 50 cc. of benzene.After 2 hours 100 cc. of water are added, the benzene layer separated,dried over sodium sulphate and evaporated. There remains crystalline[3-[9zl0- dihydro-9: l0-ethano-(l :2) 9-anthryl]-'propionic aciddimethylamide which can be used without further purification.

Example A solution of 14.0 grams of 2-chloro-anthracene-(9)- aldehyde in200 cc. of dimethyl-formamide is saturated with ethylene and then heatedin an autoclave for 24 hours at 170 C. The dimethylformamide is thendistilled off in vacuo. A viscous oil remains behind which is dissolvedin 100 cc. of ethanol; :after the addition of 10 grams ofmonomethylarnine, the reaction mixture is heated in a bomb tube for 4hon-rs at 90 C. The solution is evaporated to dryness, the residuedissolved in 200 cc. of ethanol and, after the addition of 2 grams ofRaney nickel, hydrogenated under 5 atmospheres gauge pressure. Afterfiltering off the catalyst, the reaction mixture is evaporated todryness under reduced pressure. The residue is boiled with 100 cc. of 2N-hydrochloric acid and the hydrochloric acid solution is seprated off.On cooling, an oil separates which crystallizes after being allowed tostand for some time. There is obtained 2-chlor0-9-methylamino-methyl-9:10-dihydro-9:10-ethano-(1:2)-anthracene hydrochloride of the formulain the form of white crystals which melt at 223226 C. aftercrystallization from water.

The 2-chloro-anthracene-(9)-aldehyde used as starting material may beprepared as follows:

A mixture of 42 grams of 2-chloro-anthracene, 54 grams ofN-methyl-forrna-mide, 60 grams of phosphorus oxychloride and 40 cc. ofdichloro-benzene is heated for 2 hours at 90-95 C. with stirring. Asolution of 280 grams of crystalline sodium acetate in 500 cc. of wateris then added. A precipitate settles out which is filtered off andboiled with ethanol. The hot ethanol solution is filtered. On coolingthe filtrate, 2-chloroanthracene-(9)-aldehyde separates in the form ofyellow needles which melt at 148- 150 C. after recrystallization fromglacial acetic acid.

Example 11 A solution of 5.0 grams of dimethyla-mine in 50 cc. ofbenzene is added dropwise and with stirring to 4.0 grams of 1:5dichloro-9:10-dihydro-9:10 ethano-(1:2)- anthracene-9-carboxylic acidchloride in 50 cc. of benzene at room temperature. After 2 hours, 100cc. of water are added and the benzene layer is evaporated to drynessunder reduced pressure. The residue is dissolved in 50 cc. of absolutetetrahydrofuran and the resulting solution added dropwise and withstirring to a mixture of 2.0 grams of lithium aluminium hydride and 50cc. of tetra-hydrofuran. The mixture is heated to the boil for 2 hoursand then decomposed by the addition of water and sodium hydroxidesolution of 15% strength. After filtering off the precipitate which hassettled out and evaporating the filtrate, an oil remains which isdissolved in 10 cc. of ethanol. The solution is treated with 0.5 cc. of10 N- ethanolic hydrochloric acid and the hydrochloride formed isprecipitated by the addition of diethyl ether. There is obtained 1:5dichloro-9dimethylamino-methyl-9:l0 dihydro-9: IO-ethano- (1:2)-anthracene-hydrochloride of the formula c1 ca -utca l -BC1 in theform of crystals melting at 158162 C.

The 1:5 dichloro 9:10 dihydro-9:l0-ethano-(1:2)- anthracene-9-carboxylicacid chloride used as starting material may be prepared as follows:

A solution of 12 grams of 1:S-dichloro-anthracene-(9)- carboxylic acidin 200 cc. of dimethylformamide is saturated with ethylene and thenheated rfor 24 hours at 170 C. in an autoclave. The residue whichremains after the solution has been evaporated under reduced pressure isdissolved in 2 N-sodium hydroxide solution and filtered through carbon.On acidification of the solution crude 1:5- dichloro 9:10 dihydro 9:10ethano (1:2) anthracene-9-carboxylic acid precipitates which is filteredoff and dried. 1 0 grams of this acid are boiled for 2 hours with 200cc. of thionyl chloride. When the solution has been evaporated thereremains an oil which crystallizes slowly. After recrystallization frompetroleum ether there is obtained 1:5 dichloro 9:10-dihydro-9:10-ethano-(1:2)- anthracene-9-carboxy'lic acid chloride of theformula 01 CULT melting at 132135 C.

Example 12 12 g. of fl-[9z10-dihydro-9:IO-ethano-(l:2)-anthryl]-propionyl chloride in 75 ml. of methylenechloride are stirred dropwiseinto a solution of 7 g. of fi-hydroxyethylpiperazine in 75 ml. ofmethylenechloride. The whole is stirred for 3 hours at room temperature,and the precipitate formed is then filtered off. The filtrate isevaporated and the residue dissolved in 2 N-hydrochloric acid andextracted with ether. The acidic extract is alkalinized and extractedwith methylenechloride. The methylenechloride is separated, dried oversodium sulfate and evaporated. The residue, (fit-[9: 10 dihydro 9: 10ethano-(1:2)-anthryl]-propionic acid-N'-(fl-hydroxyethy1)-piperazide),is dissolved in ml. of absolute tetrahydrofuran. This solution is addeddropwise to a suspension of 7.5 g. of lithium aluminum hydride in 100ml. of tetrahydrofuran, and the whole is heated for 2 hours at 50 C.,then cooled, whereupon 8 ml. of water, 8 ml. of 15% sodium hydroxidesolution and 24 ml. of water are successively dropped in. The resultingprecipitate is filtered off and the filtrate is evaporated under vacuum,to leave an oily residue, namely (9-[7 (N' hydroxyethylpiperazino)-propyl]- 9: 10-dihydro 9: 10 ethano-(1:2)-anthracene), whichis dissolved in 100 ml. of ethanol. On addition of 10 ml. of 10%alcoholic hydrochloric acid a precipitate is obtained which isrecrystallized from methanol, to yield 9-[7(N'-hydroxyethyl-piperazino)-propyl] 9:10 dihydro 9: ethano-(1:2)-anthracenedihydrochloride of the formula 2 HClv in white crystals melting at 266to 268 C.

This product may be incorporated, for example, in tablets of thefollowing composition:

Example 13 34 g. of fi-[9,10-dihydro-9,10-ethano-(1,2)-9-anthryl]-propionic acid monomethylamide in 150 ml. of absolute tetrahydrofuranare stirred dropwise at room temperature into a suspension of 10 g. oflithium-aluminium hydride in 250 ml. of absolute tetrahydrofuran, andthe mixture is heated for 3 hours at 60 C. and then cooled to 10 C. 10ml. of water and 10 ml. of sodium hydroxide solution are then dropped inand the precipitate formed is filtered OH. The filtrate is evaporatedunder vacuum, to leave an oil which is dissolved in 50 ml. of ethanol.On addition of 10 N-ethanolic hydrochloric acid and ether, the 9('y-methylaminopropyl)-9,10-dihydro-9,10- ethano-(l,2)-anthracenehydrochloride of the formula precipitates in the form of white crystalswhich melt at 230 to 232 C. after recrystallization from isopropanol.

The B-[9,10-dihydro-9,10-ethano-(1,2)-9-anthryl]-propionic acidmonomethylamide used as starting material can be prepared in thefollowing manner:

While cooling a solution of 50.0 g. of B-[9,10-dihydr-o-9,il0-ethano-(l,2)-9-anthryl]-propionylchloride in /2 liter ofmethylenechloride about g. of monomethylamine is I introduced into it inthe course of one hour. 200 ml. of water are then added, themethylenechloride layer is separated, dried over sodium sulphate and thesolvent is distilled ofi, to yield B-[9,l0-dihydro-9,l0-ethano-(1,2)-9-anthryl1-propionic acid monomethylamide which melts at 158 to 161 C.after recrystallization from a mixture of methylenechloride+petroleumether.

Tablets, each containing mg. of active principle, can be prepared, forexample, from the following ingredients:

Example 14 A solution of 6.8 g. of fi-[l0-chloro-9,l0-dihydro-9,l0-ethano-(l,2)-9-anthryl]-propionic acid dimethylarnide in ml. of absolutetetrahydrofuran is stirred dropwise into a suspension of 2.5 g. oflithium-aluminium hydride in 60 ml. of absolute tetrahydrofuran. Themixture is then heated for 3 hours at C., cooled to room temture and 12ml. of water are cautiously added. The precipitate formed is filteredoff, and the filtrate evaporated under vacuum, the oily residuedissolved in ether and the ethereal solution is extracted with 2N-hydrochloric acid. The acid solution is alkalinized with 10 N-sodiumhydroxide solution and the precipitated base is extracted with ether.The extract is dried and evaporated, to leave 9-7- dimethylaminopropyl10 chloro 9,10 dihydro 9,10- ethano-(l,2)-anthracene of the formula or:CH2 ca ca n 5 cH whose hydrochloride melts at 225226 C.

The 18-[10 chloro 9,10 dihydro-9,10-ethano-(1,2)-9- anthrylJ-propionicacid dimethylarnide used as starting material can be prepared in thefollowing manner:

30 grams of 10-chloro-9-anthraldehyde are stirred into a suspension of 8g. of sodium borohydride in 200 ml. of ethanol. After 1 hour 150 ml. ofwater are added. A precipitate is formed which is filtered off andrecrystallized from dimethylformamide+methanol, to yield crystalline9-hydroxymethyl 10 chloroanthracene melting at 203- 205 C.

26 grams of 9-hydroxymethyl-l0-chloroanthraceue are mixed with 14 g. ofthionylchloride in 100 ml. of dioxan and refluxed for 2 hours. Aftercooling, 9-chloromethyl- 10-chloroanthracene precipitates in crystallineform. After recrystallization from hexane the compound melts at 168-170C.

16 grams of malonic acid diethyl ester are added to a suspension of 2.5-g. of sodium hydride in 300 ml. of benzene and the whole is heated for2 hours at C. 24 grams of 9-chloromethyl-lO-chloroanthracene are addedand the mixture is refluxed for 7 hours. 200 ml. of Water are then addedat room temperature and the benzene layer is separated. Afterevaporation of the solvent 1-(10-chloro-9-anthryl) 2,2ethanedicarboxylic acid diethyl ester is obtained; afterrecrystallization from isopropanol it melts at 88-93 C.

When 27 g. of this ester are boiled in a solution of 80 ml. of 2N-sodium hydroxide solution and ml. of alcohol and then acidified with 5N-hydrochloric acid, there is obtained the1-(l0-chloro-9-anthryl)-ethane-2,2- dicarboxylic acid (melting at 216C.) which on heating to 220 C. gives rise toB-(l0-chloro-9-anthryl)-propionic acid by decarboxylation; this compoundmelts at 190- 19g? C. after recrystallization from dioxan-l-petroleum eter.

A solution of 12 g. of B-( l0-chloro-9-anthryl)-propionic acid in 250 g.of toluene is heated in an autoclave with ethylene for 20 hours at 170C. On cooling, crystalline B-[10-chloro-9,10-dihydro-9,l0-ethano-(l,2)-9anthryl]- propionic acid melting at 280 C. is obtained.

8 grams of this acid are heated for 2 hours with 80 ml. ofthionylchloride. On evaporation of the excess thionylchloride,,8-[l0-ch10ro-9,l0-dihydro-9,10-ethanol- 1,2)-9- anthryl]-propionic acidchloride is obtained which melts at 150 C. after recrystallization fromhexane.

Dimethylamine is injected for one hour into a solution of 7.5 g. of theacid chloride in 75 ml. of benzene. The precipitate formed is filteredoff and the filtrate evaporated under vacuum, to leave a residue whichis recrystallized from ether, to yield B-[lO-chloro 9,10 dihydro-9,10-ethano-(l,2)-9-anthryl]-propionic acid dimethylarnide in crystalsmelting at 143-147 C.

13 Example 15 17 grams of ,8-[2-chloro-9,10-dihydro-9,10-ethano-(l,2)-9-anthryl]-propionic acid dimethylamide in 100 ml. of absolutetetrahydrofuran are stirred dropwise into a suspension of 5 g. oflithiumaluminium hydride in 100 ml. of absolute tetrahydrofuran, and themixture is stirred for 5 hours at 60 C., then cooled and 20 ml. of waterare added. The precipitate formed is filtered oil and the filtrateevaporated under vacuum, to leave a oil which is mixed with 2 ml. of Nhydrochloric acid in alcohol and ether, to yield2-chloro-9-'y-dimethylaminopropyl-9,lO-dihydro-9,l0-ethano-(1,2)-anthracene hydrochloride of the formula which melts at171-173 C. after recrystallization from isopropanol.

The fi-[2chl0r0-9,10-dihydro 9,10 ethano-(l,2)-9- anthrylJ-propionic:acid dimethylamide used as starting material is obtained by the methodsdescribed in Example 14 from 2-chloroanthracene-(9)-aldehyde via -HClExample 16 A solution of 30 g. of fl-[chloro-9,l0-dihydro-9,l0ethano-(l,2)-9-anthryl]-propionic acid dimethylamide in 200 ml. ofabsolute tetrahydrofuran is stirred dropwise under nitrogen into asuspension of 6 g. of lithium-aluminium hydride in 200 ml. of absolutetetrahydrofuran. The reaction mixture is refluxed for 2 hours, cooled,and 6 ml. of water, 6 ml. of sodium hydroxide solution of strength and18 ml. of water are added. The whole is completely evaported and theresidue dissolved in 200 ml. of 2 N-hydrochloric acid, the solutionextracted with ether and the residual aqueous phase is rendered clearlyalkaline with concentrated sodium hydroxide solution while being cooled,and extracted with ether. The ethereal extracts are dried over sodiumsulphate and evaporated to form an oily residue which is once moredissolved in ether and mixed with the calculated amount of maleic acidin ether, to yield a crystalline maleate of the formula CH ca ca on N/01 HCCOOH which melts at 154-156" C. after recrystallization fromethanol+ether.

The lit-[3 chloro-9,10-dihydro-9,10-ethano (l,2)-9- zinthryH-propionicacid dimethylamide used as starting material is obtained in oily formfrom B-(3-chloro-9-anthryl)-propi0nic acid (melting at 189-190 C.) byreaction with ethylene oxide to form fi-[3-chloro-9,10-dihydro- 149,10-ethano-(1,2)-9-anthryl]-propionic acid (melting at 197-199 C.),conversion with thionylchloride into the acid chloride and reaction withdimethylamine.

Example 17 A solution of 25 g. of 5-[3-chloro-9,10-dihydro-9,10-ethano-(1,2)-9-anthryl]-propionic acid monomethylamide in 200 ml. ofabsolute tetrahydrofuran is stirred dropwise under nitrogen into asuspension of 6 g. of lithiumaIuminium hydride in 200 ml. of absolutetetrahydrofuran. The reaction mixture is refluxed for 2 hours, cooled,and 6 ml. of water, 6 ml. of sodium hydroxide solution of 15% strengthand 18 ml. of water are added. The batch is completely evaporated undervacuum, the residue dissolved in 500 ml. of 2 N-hydrochloric acid, thesolution extracted with ether and the aqueous residue rendereddistinctly alkaline with concentrated sodium hydroxide solution whilebeing cooled, and then extracted with ether. The ethereal extracts aredried over sodium sulphate and evaporated, to yield3-chloro-9-('y-monomethylaminopropyl)-9,10-dihydro-9,10-ethano-l,2-anthraceneof the formula The B[3-chloro-9,10-dihydro-9,l0-ethano-(l,2)-9-anthryl]-propionic acidmonomethylamide used as starting material is obtained in oily form frommethylamine as described in Example 16.

Example 18 A solution of 23 g. of 2-chloro-9-methylaminomethyl-9,10-dihydro-9,10-ethano-(1,2)-anthracene (cf. Example 10) in 100 ml. offormic acid and 10 ml. of Formalin of 30% strength is heated for 4 hoursat C. /2 liter of water is then added and the whole is rendered alkalinewith 10 N-sodium hydroxide solution. The precipitating oil is extractedwith ether. The ether extract is dried and evaporated, to yield2-chloro-9-dimethylaminomethyl-9,10-dihydro-9,10-ethano-(1,2)-anthracene of the formula whosehydrochloride melts at 244-245 C.

Example 19 7 grams of N-acetyl-2-chloro-9-ethylaminomethyl-9,10-dihydro-9,l0-ethano-(1,2)-anthracene in 50 ml. of absolutetetrahydrofuran are dropped into a suspension of 2 g. oflithium-aluminium hydride in 50 ml. of absolute tetrahydrofuran and thewhole is stirred for 4 hours at 50 C., then cooled to room temperature,and 15 ml. of water are cautiously added. The precipitate formed isfiltered off and the filtrate evaporated under vacuum to dryness, toleave an oil which is dissolved in 10 ml. of ethanol. On addition of 1.5ml. of 10 N-hydrochloric acid in alcohol and ether, the hydrochloride of2-chloro-9-diethylaminoethyl- 9,10-dihydro-9,10-ethano-(1,2)-anthraceneof the formula settles out in white crystals melting at 231 C.

15 The N-acetyl 2-chloro 9-ethylaminomethyl9,10-dihydro-9,10-ethan-(1,2)-anthracene used as starting material maybe obtained by reacting2-chloro-9-ethylaminomethyl-9,10-dihydro-9,10-ethano (l,2)-anthracene[prepared with ethylamine, as described in Example 10] with aceticanhydride at ll0120 C. for 5 hours.

Example 20 A mixture of 36 g. of -chloro-9,l0-dihydro-9,l0-ethano-(1,2)-9-anthracene aldehyde and a saturated ethanolic solution ofethylamine is heated in an autoclave for 5 hours at 80 C., whereupon thesolution is evaporated under vacuum.

The residue is dissolved in 250 ml. of ethanol, 5 g. of Raney nickel areadded, and the mixture is hydrogenated at room temperature. After thecatalyst has been filtered off and the solvent evaporated, there remains9-ethyl-aminomethyl-l0-chloro-9,IO-dihydro 9,10-ethanoanthracene of theformula 7" 1 CIEH LHC 11 which melts at 88-91 C. after recrystallizationfrom hexane. The hydrochloride melts above 300 C.

Example 21 A solution of 14 g. of N-acetyl-9-ethylaminomethyl-10-chloro-9,l0-dihydro-9,10-ethano-(l,2)-anthracene in 50 ml. of absolutetetrahydrofuran is dropped into 5 g. of lithium-aluminium hydride in 100ml. of absolute tetrahydrofuran, and the batch is then heated for 4hours at 60 C, whereupon ml of Water are cautiously added at roomtemperature The precipitate formed is filtered off and the filtrateevaporated to dryness under vacuum, to yield 9-diethylarninomethyll0-chloro-9,l0-dihydro 9,10- ethano-(l,2)-anthracene of the formulawhich melts at 1l61l8 C after recrystallization from ethanol. Itshydrochloride melts at 200-205 C.

TheN-acetyl-9-ethylaminomethyl-10-chloro-9,10-dihydro-9,l0-ethano-(1,2)-anthraceneused as starting material may be prepared by reacting9-ethylaminomethyl- 10-chloro-9, l 0-dihydro-9, 1 O-ethano- 1,2-anthracene (cf. Example 18) with acetic anhydride at 110 C. Thecompound melts at 203-205" C.

Example 22 13 grams of 9-dimethylaminomethyl-9,l0-dihydro-9,10-ethano-(1,2)-anthracene are stirred into a mixture of 100 ml. ofconcentrated sulphuric acid and 10 ml. of concentrated nitric acid, andthe mixture is heated for 1 hour at 60 C., then poured over ice andrendered alkaline with 10 N-sodium hydroxide solution. On extractionwith methylenechloride, drying and evaporation, a solid residue isobtained which is recrystallized from alcohol, to

16 yield 1,3,6-trinitro 9-dimethylaminomethyl-9,IO-dihydro-9,Il0-ethano-(l,2)-anthracene of the formula in yellow crystals meltingat 183-184 C.

What is claimed is:

1. A member selected from the group consisting of (a) compounds of theformula Ph Ph' wherein alk represents a lower alkylene radicalcontaining at most 4 carbon atoms, R stands for a member selected fromthe group consisting of hydrogen, halogen and lower alkyl, and R and Reach represents a member selected from the group consisting of hydrogen,lower alkyl, lower hydroxyalkyl, lower monooxaalkyl, lower monoazalkyl,lower monothiaalkyl, lower alkenyl, cyclo-lower alkyl, cyclo-loweralkyl-lower akyl, Ph-lower alkyl, and, when taken together with thenitrogen atom a 5-7 membered alkylene imino ring; a saturated 5-7membered 4-aza alkylene imino ring in which the aza nitrogen isunsubstituted or substituted by a member selected from the groupconsisting of lower-alkyl, hydroxy lower alkyl; and morpholino, andwherein Ph and Ph each represents a member selected from the groupconsisting of 1,2-phenylene, lower alkyl-1,2-phenylene, lower alkoxy-1,2 phenylene, halogeno 1,2-phenylene, t-rifluoromethyl- 1,2-phenylene,nitro-l,2aphenylene and amino-1,2-phenylene, and Ph stands for a memberselected from the group consisting of phenyl, lower alkoxy-phenyl, loweralkyl-phenyl, halogeno-phenyl, trifiuorornethyl-phenyl, andamino-phenyl, and the lower alkyl and alkenyl portion in saidsubstituents contain at most 7 carbon atoms and the cycloalkyl portionsin said substituents contain from 4 to 7 ring carbon atoms, b) theirquaternary lower alkyl, lower alkenyl, Ph"-methyl and phenoxy-loweralkyl derivatives wherein the lower alkyl and alkenyl portions containat most 7 carbon atoms and Ph stands for a member selected from thegroup consisting of phenyl, lower alkoxy-phenyl, lower alkyl-phenyl,halogenophenyl, trifiuoromethyl-phenyl, and amino-phenyl, and the loweralkyl and alkenyl portion in said substituents contain at most 7 carbonatoms and the cycloalkyl portions in said substituents contain 4 to 7ring carbon atoms, and (c) t-heir acid addition salts.

2. A compound as claimed in claim 1 having the formula a member selectedfrom the group consisting of 1,2-phenylene, lower alkyl-1,2-phenylene,lower alkoxy-1,2-phenylene, halogeno 1,2 phenylene andtrifluoromethyl-LZ- phenylene, the lower alkyl portions in said radicalscontaining at most 7 carbon atoms, said compound being in a formselected from the free form and the form of an acid addition saltthereof.

3. A compound as claimed in claim 1 being in the form of atherapeutically useful acid addition salt.

4. A therapeutically useful acid addition salt of a compound having theformula indicated in claim 2.

5. A compound as claimed in claim 1 and having the formula c: R ga.

wherein alk is a lower alkylene radical with at most 4 carobn atoms, Ris a member selected from the group consisting of hydrogen and loweralkyl and R is a lower alkyl radical and each of the radicals Ph and Phis a member selected from the group consisting of 1,2-phenylene andhalogeno-l,2-phenylene.

6. A therapeutically useful acid addition salt of a compound having theformula indicated in claim 5.

7. A compound as claimed in claim 1 and having the formula alk "Awherein alk is a lower alkylene radical with at most 4 carbon atoms, Ais a member selected from the group consisting of N-loweralkyl-piperazino and N-(hydroxy-lower alkyl)-piperazino and each of theradicals Ph and Ph is a member selected from the group consisting of1,2-phenylene and halogeno-l,2-pheuylene.

8. A therapeutically useful acid addition salt of a compound having theformula indicated in claim 7.

9. A compound as claimed in claim 1 and having the formula wherein R islower alkyl and alk a lower alkylene radical with at most 4 carbonatmos, said compound being in a form selected from the free form and theform of a. therapeutically useful acid addition salt thereof.

10. A compound as claimed in claim 1 and having the formula wherein Rand R each represents a lower alkyl radical and alk represents a loweralkylene radical with at most 4 canbon atoms, said com-pound being in aform selected from the free form and the form of a therapeuticallyuseful acid addition salt thereof.

t 11. A compound as claimed in claim 1 and having the formula wherein Ris a lower alkyl radical, said compound being in aform selected from thefree form and the form of a therapeutically useful acid addition saltthereof.

12. A compound as claimed in claim 1 and having the formula )1 (Gri -N Rwherein n is l or 3 and R is a member selected from the group consistingof hydrogen and lower alkyl and R is lower alkyl, said compound being ina form selected from the free form and the form of a therapeuticallyuseful acid addition salt thereof.

13. A compound as claimed in claim 1 being a member selected from thegroup consisting of 9-methylaminomethyl-9a10-dihydro-9:IO-ethano-(l:2)-anthracene and a therapeutically useful acid additionsalt thereof.

14. A compound as claimed in claim 1 being a member selected from thegroup consisting of 9-n-butylaminomethyl-9:l0-ethano-(1:2)-anthraceneand a therapeutically useful acid addition salt thereof.

15. A compound as claimed in claim 1 being a member selected from thegroup consisting of 9-dimethylamino methyl 9:10 dihydro 9:10 ethano(1:2)- anthracene and a therapeutically useful acid addition saltthereof.

16. A compound as claimed in claim 1 being a member selected from thegroup consisting of 9-diethylaminomethyl 9:10 dihydro 9:10 ethano (1:2)anthracene and a therapeutically useful acid addition salt thereof.

17. A compound as claimed in claim 1 being a member selected from thegroup consisting of 9-(methyl-ethylamino methyl) 9:10 dihydro 9:10ethano (1:2)- anthracene and a therapeutically useful acid addition saltthereof.

18. A compound as claimed in claim 1 being a member selected from thegroup consisting of 9-(N-methyl-N- n butylamino methyl) 9: l0 dihydro 9:l0 ethano- (1:2)-anthracene and a therapeutically useful acid additionsalt thereof.

19. A compound as claimed in claim 1 being a member selected from thegroup consisting of 9- -dimethylamino propyl 9:10 dihydro 9:10 ethano(1:2)- anthracene and a therapeutically useful acid addition saltthereof.

20. A compound as claimed in claim 1 being a member selected from thegroup consisting of 9-( -methylamino propyl) 9,10 dihydro 9,10 ethano(1,2)- anthracene and a therapeutically useful acid addition saltthereof.

21. A compound as claimed in claim 1 being a member selected from thegroup consisting of 2-chloro-9-methylamino methyl 9: 10 dihydro 9:10ethano (1 :2)- anthracene and a therapeutically useful acid additionsalt thereof.

22. A compound as claimed in claim 1 being a member selected from thegroup consisting of 2-chloro9-('ydimethylaminopropyl) 9:10 dihydro 9:10ethano- (1:2)-anthracene and a therapeutically useful acid addition saltthereof.

23. A compound as claimed inclaim 1 being a member selected from thegroup consisting of 2-chloro-9-di- 19 methylaminornethyl 9:10 dihydro9:10 ethano- (1:2)-anthracene and a therapeutically useful acid additionsalt thereof.

24. A compound as claimed in claim 1 being a member selected from the'group consisting of 2-chloro-9-diethylarninomethyl 9:10 dihydro 9:10ethano (1:2)- anthracene and a therapeutically useful acid addition saltthereof.

25. A compound as claimed in claim 1 being a member selected from thegroup consisting of lO-chloro-9- ethylaminomethyl 9: 10 dihydro 9: 10ethano (1:2)- anthracene and a therapeutically useful acid addition saltthereof.

No references cited.

HENRY R. JILES, Primary Examiner.

Disclaimer 3,399,201.Paul Schmidt, Therwil, Max Wilhelm, Allschwil, andKurt Eichenberger, Therwil, Switzerland. AMINOALKYL-ETHANO-AN-THRACENES. Patent dated Aug. 27, 1968. Disclaimer filed Oct. 22, 1984,by the assignee, Ciba-Geigy Corp. Hereby enters this disclaimer toclaims 1-19 and 21-25 of said patent.

[Official Gazette December I], 1984.]

1. A MEMBER SELECTED FROM THE GROUP CONSISTING OF (A) COMPOUNDS OF THEFORMULA